Two proven cancer drugs traditionally used to treat Ewing’s Sarcoma, Metastatic Breast Cancer and Leukemia are now being tested by researchers to determine if they can be repurposed to fight drug-resistant gastrointestinal stromal tumors (GISTs). University of Pittsburgh Cancer Institute (UPCI) scientists are currently engaged in finalizing a high-profile study that will be published in the journal Cancer Research, demonstrating that through a high-throughput screening process, FDA-approved cancer drugs can indeed treat GISTs that are not responding to front-line therapies.

Anette Duensing, M.D., assistant professor of pathology at UPCI and researcher at the center of the study, is calling this new approach “drug repurposing:” “. . . it is an increasingly promising way to speed up the development of treatments for cancers that do not respond well to standard therapies. Drug repurposing builds upon previous research and development efforts, and detailed information about the drug formulation and safety is usually available, meaning that it can be ready for clinical trials much faster than a brand-new drug.”

By screening 89 drugs previously approved by the FDA for a wide range of cancer types, Duensing and her team used the data to find new treatment options for (GISTs), which, while uncommon, have proven to be difficult to treat, as they begin in the walls of the gastrointestinal tract. The American Cancer Society estimates that approximately 5,000 cases of GISTs occur each year in the United States, with an estimated five-year survival rate of 45 percent in patients with advanced disease.

Oncologists traditionally use the targeted therapy drug imatinib, known by the trade name Gleevec, to treat GISTs, which are the result of a single gene mutation. Imatinib has been shown to be effective in treating GISTs, however, after two years of treatment with Gleevec, roughly half of GIST patients become resistant to the drug. The idea behind Duensing’s study is to discover a second stage of treatment for GISTs in the event that imatinib becomes ineffective.

Duensing and her team have narrowed down the scope of their study to focus on two main cancer therapies as lead candidates for GISTs: gene transcription inhibitor mithramycin A, which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone, which is used in metastatic breast cancer and leukemia. Researchers are optimistic about the viability of these two drugs, due to the fact that both drugs were highly effective in fighting GIST in laboratory tests, and the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

“These are very encouraging results,” said Duensing. “The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients.”

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